1. Field of the Invention
This invention relates to noninvasive determination of fluid density including the density of blood and hematocrit in a living subject.
2. Discussion of the Related Art
Hematocrit, an important clinical parameter, is the ratio of red blood cell volume to whole blood volume, and is often expressed as a fraction or a percent. In current medical practice the hematocrit can only be determined by invasive methods that first require drawing blood from the living subject, and then use a centrifuge or optical instrument on the raw blood to determine the hematocrit value.
Because current hematocrit monitoring techniques are invasive they expose both the caregiver and the patient to the risks of blood-borne diseases such as AIDS and hepatitis. In addition to causing discomfort to the patient and risk to the caregiver, they are also time consuming to administer, and may result in delays in treatment while results are being processed.
The primary current clinical method for determining hematocrit is the centrifuge method, e.g., U.S. Pat. No. 3,957,197. This method requires drawing a blood sample, and relies upon the differences in density of the component parts of blood (red blood cells and plasma). The centrifuge rapidly spins the blood in a tube, causing the denser parts of the blood (red blood cells) to go to the bottom of the tube, and the less dense parts (plasma) to stay near the top of the tube. After a sufficient amount of spin time (usually several minutes) has elapsed during centrifuging of the blood, all of the red blood cells are packed into the bottom of the tube with the plasma riding on top of the cells. If the length of the tube is calibrated to volume percent increments, the clinician can simply read the value of “Packed Cell Volume” from the side of the tube at the top of the cell region. “Packed Cell Volume” is slightly different from “hematocrit,” since the method of centrifuging does not perfectly pack the cells into the bottom of the tube. This leaves small spaces within the cell area of the tube for plasma to reside, resulting in an approximate 4% to 5% error between the Packed Cell Volume and the true hematocrit value. However, clinicians generally use Packed Cell Volume and Hematocrit synonymously.
Discussion of the Related Art for Non-Invasive Hematocrit
Various inventions have been disclosed, e.g., U.S. Pat. Nos. 5,978,691; 5,983,120; 5,836,317; 5,833,602, 5,803,908; 5,755,226; 5,720,284; 5,642,734; 5,564,418; 5,553,615; 5,526,808; 5,499,627; 5,487,384; 5,456,253; 5,372,136; 5,351,686; 5,277,181, and 5,101,825, which describe methods for measuring the hematocrit by noninvasive means. No noninvasive hematocrit monitor has yet become commercially available. Four basic methods have been disclosed in the art for noninvasively measuring hematocrit in a living body;                1) Optical sensing of the hemoglobin versus methemoglobin and plasma. This technique measures the relative extinction coefficients at various wavelengths of light to determine the concentration of hemoglobin versus other constituent parts of whole blood (U.S. Pat. Nos. 5,833,602 and 5,803,908);        2) Impedance sensing of the body at various select frequencies. The change of impedance values from low to high frequencies determines hematocrit from the relationship of those values (U.S. Pat. Nos. 4,547,735 and 5,526,808);        3) Reflected Imaging Analysis. This technique visually counts red blood cells in the vessel of a patient in-vivo, and determines the hematocrit by volume analysis (U.S. Pat. No. 5,983,120);        4) Mass change in hemoglobin resulting from a measured change in volume of blood (U.S. Pat. No. 5,101,825).Each of these methods measures attributes of component parts of the blood in-vivo and calculates the hematocrit from the relative values obtained. None of the prior art methods noninvasively determine the density of the whole blood in-vivo.        
Method 1 has as confounding factors the variances in light extinction due to fluid volume and skin pigmentation that adversely affect the accuracy and repeatability of the method. Method 2 uses the variation of complex impedance versus frequency to determine the relative concentration of Erythrocytes to whole blood. The confounding factor of this method is the variability of Erythrocyte cell wall thickness across a population of healthy and unhealthy patients. Since the complex impedance method is dependent on the cell wall capacitance, any variation in mean cell wall thickness has a marked affect on the total capacitance contributed by any single cell in solution. Variations in capacitance versus frequency are affected by various disease states of the patient and will contribute substantially to the inaccuracy of the measurement for these patients. Method 3, e.g., U.S. Pat. No. 5,983,120, is mechanically cumbersome to apply to the patient since the probe must be applied under the tongue of the patient for an extended period of time in order to make the measurement. This method is discomforting to a broad population of patients. Method 4, e.g., U.S. Pat. No. 5,101,825, has difficulty calibrating to the patient since the value of ΔV (the change in blood volume over time) is difficult to quantify by optical means.